Revised program will analyze the once-daily oral combination of doravirine 100 mg and a lower dose of islatravir in adults with HIV-1 infection.
Merck has announced the initiation of a new phase 3 clinical trial evaluating once-daily oral islatravir for HIV-1 infection. The revised program will analyze the once-daily oral combination of doravirine 100 mg and a lower dose of islatravir (DOR/ISL).
In one of the trials, DOR/ISL will be analyzed in previously untreated adults with HIV-1 infection, whereas 2 studies will evaluate switching to DOR/ISL from antiretroviral therapy (ART) in virologically suppressed patients with HIV-1 infection. Some patients who are currently enrolled in once-daily treatment studies with DOR 100 mg/ISL 0.75 mg will be able to shift to a new study with the lower dose of islatravir.
The investigational new drug application (IND) for once-daily oral DOR/ISL is under a partial clinical hold for any studies using doses higher than that being studied in the new phase 3 clinical trial program. The clinical hold was based on observed reductions in total lymphocyte and CD4+ T-cell counts in some patients administered islatravir in clinical studies. Merck halted dosing in the phase 2 IMAGINE-DR clinical trial of islatravir with MK-8507 (MK-8591-013) and paused enrollment in the once-monthly phase 3 PrEP studies, MK-8591-022 and MK-8591-024.
The phase 2 clinical trial (NCT05052996) studying the investigational, oral, once-weekly combination of islatravir plus lenacapavir in virologically suppressed adult patients with HIV-1 infection will resume under an amended protocol with a lower dose of islatravir.
The IND for the islatravir plus lenacapavir combination is still under a partial clinical hold for any studies using weekly oral islatravir doses higher than those under consideration for the revised clinical program. The islatravir plus lenacapavir combination has not been approved for use by the FDA and the safety and efficacy of the combination has yet to be established.
Merck also announced that is discontinuing the development of once-monthly oral islatravir for PrEP. Patients in the ongoing phase 3 PrEP once-monthly oral studies will continue to be monitored.
“We are grateful to the study investigators and the many participants in the trials of islatravir. Following extensive evaluations and consultation with FDA, we are pleased to be able to initiate our new Phase 3 clinical program to evaluate islatravir for the treatment of HIV-1 infection,” said Eliav Barr, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in a press release. “We continue to believe in the potential of the NRTTI mechanism and we are evaluating additional candidates with the goal of helping to address unmet needs in HIV prevention. As part of this, we are pleased to continue our partnership with the Bill & Melinda Gates Foundation as we continue to evaluate potential long-acting PrEP opportunities.”
Merck to Initiate New Phase 3 Clinical Program with Lower Dose of Daily Oral Islatravir in Combination with Doravirine for Treatment of People with HIV-1 Infection. Merck. News release. September 20, 2022. https://www.merck.com/news/merck-to-initiate-new-phase-3-clinical-program-with-lower-dose-of-daily-oral-islatravir-in-combination-with-doravirine-for-treatment-of-people-with-hiv-1-infection/